Total parenteral nutrition (TPN) solutions either exposed to light (+L) or protected from light (-L) were infused for 5 days through jugular cannulas in freely moving rats placed in metabolic cages. At the end of the 5 day period, bile flow, biliary inorganic phosphate and biliary γ-glutamyl transferase activity, as well as biliary concentrations of several essential and branch chain amino acids were significantly lower in the -L animals compared to +L animals. In addition, biliary glutathione was significantly lower in the +L animals. In both groups of animals, plasma tyrosine decreased significantly from pre-TPN values despite a doubling of plasma phenylalanine concentrations suggesting that tyrosine may become a conditionally essential amino acid in rats provided TPN. Our findings indicate that short-term parenteral infusion of light exposed TPN solutions alters hepatobiliary function as well as amino acid homeostasis and that the changes are minimized by light protection of the infusates. The exact mechanisms of the contribution of light exposure in the induction of hepatic dysfunction remain to be elucidated. Total parenteral nutrition (TPN) has been clearly associated with hepatobiliary complications in infants, children and adults (Fisher, 1989; Balistreri and Bove, 1990). The etiology of TPN-induced hepatobiliary complications is poorly understood and is most likely multifactorial (for review see Balistreri and Bove, 1990). Factors postulated to be associated with this complication include: photootoxidation products of amino acids (Grant et al., 1977; Merritt et al., 1984; Bhatia and Rassin, 1985; Donoso et al., 1988); excessive intake of amino acids (Vileisis et al., 1980); essential fatty acid deficiency (Keim et al., 1987); depletion of tissue glutathione (Heyman et al., 1986); excessive carbohydrate intake (McKenna et al., 1982; Chang and Silvis, 1974; Martins et al., 1985; Buzby et al., 1981; Tulikoura and Huikuiri, 1982) and starvation (Beale et al., 1979; Rager and Finegold, 1975). Our laboratory has focused on the possible detrimental role of light exposure for three reasons: 1) Photooxidation of amino acids has long been recognized. 2) Experiments in animals given light-exposed amino acids have demonstrated an association between photooxidation of amino acids and hepatic dysfunction. 3) TPN mixtures are continually exposed to light from various sources during infusion. The amino acids that are most susceptible to photooxidation are cysteine, histidine, methionine, tryptophan and tyrosine (Weil, Gordon, and Buchert, 1951; Gurnani and Arifuddin, 1966; Gurnani, Arifuddin, and Augusti, 1966; Benassi et al., 1967). Administration of light- exposed tryptophan especially in the presence of a photosensitizing agent (riboflavin) leads to hepatic dysfunction in young gerbils (Bhatia and Rassin, 1985) and in rats (Merritt et al., 1984; Donoso et al., 1988). Grant and coworkers (1977) studied rats receiving TPN regimens for 10d which contained tryptophan that was previously exposed to room light resulting in 'conversion products' or freshly added tryptophan. Rats receiving the TPN solutions containing 'conversion products' had fatty changes in periportal hepatocytes and increased serum activity of enzymes reflective of hepatic dysfunction. These authors thus suggested that to avoid possible TPN- associated hepatotoxicity, amino acid solutions be 'placed immediately into amber bottles after addition of tryptophan or in some manner protected from light until used'. Currently, however, parenteral amino acid preparations are marketed in clear bottles and, after addition of dextrose, vitamins, trace metals, minerals and electrolytes, are infused through clear tubing without protection from light; light exposure is particularly high in intensive care nurseries which have fluorescent as well as other light sources on around the clock. Similarly, in the ambulatory setting these solutions may be exposed to sun light. These light sources would thus promote photooxidation of amino acids with formation of either photoxidized compounds (Bhatia et al., 1983) or photo-adducts (Donoso et al., 1988). The present study was undertaken to test the hypothesis that protection of TPN constituents from light would decrease the hepatic dysfunction associated with TPN.
|Original language||English (US)|
|Number of pages||20|
|Journal||Research Communications in Chemical Pathology and Pharmacology|
|State||Published - 1992|
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Pharmacology, Toxicology and Pharmaceutics(all)